Assembly for Heat Treating Biological Tissue

ABSTRACT

An assembly for heat treating an area of biological tissue, including energy generating means for supplying energy to a focal point in said area, means for measuring the spatial temperature distribution in said area, and a control unit for controlling the movement of the focal point along a predetermined path to give a spatial temperature distribution consistent with a pre-sent distribution, characterized in that, as the focal point moves along the path, the control unit controls the distribution of the energy provided by the generating means depending on the measured temperature distribution and the pre-set distribution, in accordance with a control law including a proportional-integral-derivative term.

The area of the invention relates to the treatment of biological tissuesby hyperthermia.

Hyperthermia therapies are techniques routinely used for the localtreatment of biological tissues. They consist of heating a target areaof the biological tissue using an energy source (laser, microwave,radiofrequency waves, ultrasound).

Generally, therapy by local hyperthermia allows medical treatment withminimum invasion. Among the types of energy used, focused ultrasound(FUS) is of particular interest since it enables a target area to beheated non-invasively and in-depth in the tissues.

During the treatment, the temperature of the target area and itsimmediate surrounding area must be precisely and continuously monitored.However the rise in temperature generated by ultrasound in tissues isdifficult to assess since this temperature rise is dependent onbiological and physiological characteristics (absorption, heatdiffusion) of the tissue in the target area.

Document FR 2 823 678 (published on 25 Oct. 2002) describes an assemblyfor heat treatment which can be used for automatic temperature controlin a target area of the tissue to be treated. The assembly comprises anultrasound generator, MRI imaging means to measure and record spatialtemperature distribution in the target region, and a control unitcomprising dot-by-dot digital processing means of spatial temperaturedistribution. The control unit commands the movement in space of theultrasound generator in relation to temperature distribution measured byimaging means so that the temperature in the target region follows a settemperature profile.

The document “Local hyperthermia with MR-guided focused ultrasound:Spiral trajectory of the focal point optimized for temperatureuniformity in the target region”, Journal of Magnetic Resonance Imaging,12: 571-583 (published in 2000) describes a treatment method usingfocused ultrasound whose purpose is to obtain uniform temperature risein a target region of large volume. According to this method, the focalpoint of an ultrasound generator is moved along a first spiral-shapedtrajectory. Spatial temperature distribution in the target region ismeasured by MRI. In relation to the spatial distribution obtained, asecond spiral trajectory is determined in which the speed of movement ofthe focal point is modified to offset non-homogeneities in temperaturedistribution remaining after the first trajectory. The focal point ofthe ultrasound generator is moved along this second trajectory.

However, said method is based on linear modelling of tissue behaviour.Yet some tissues may have non-linear behaviour, in particular withrespect to their heat conduction characteristics. This may result inunstable temperature servo-control.

One purpose of the invention is to provide a stable treatment device,having good tolerance to estimation uncertainties regardingphysiological parameters.

For this purpose, the invention proposes a heat treatment assembly fortreating a biological tissue region comprising:

-   -   energy generating means to supply energy at a focal point of the        region,    -   means for measuring spatial temperature distribution in said        region,    -   a control unit able to command movement of the focal point along        a predetermined trajectory with a view to obtaining a spatial        distribution of temperature conforming to a set distribution.

characterized in that during the displacement of the focal point, thecontrol unit is able to command the distribution of energy supplied bythe generator means along the length of the trajectory in relation tomeasured temperature distribution and set distribution, in accordancewith a control law comprising a Proportional-Integral-Derivative term.

The control law used in this treatment assembly makes it possible toreach a pre-defined set temperature profile in an extended targetregion, in spite of any non-linear physiological effects duringtreatment.

In one embodiment of the treatment assembly, the control unit is able tocommand the movement of the focal point along a series of successivetrajectories and for each trajectory to command corresponding energydistribution, in relation to a set distribution associated with thistrajectory and to temperature distributions measured throughout thepreceding trajectories.

In this embodiment, the control unit is able to command the movement ofthe focal point along a first trajectory and to deduce thereupon, inrelation to the measured temperature rise, a thermal diffusioncoefficient D in the target region. The control unit is able to takethis thermal diffusion coefficient into account in the control law.

In one embodiment of the invention, to command energy distribution, thecontrol unit is able to determine a distribution function defining theposition of the focal point along the trajectory in relation to time.

In one embodiment of the invention, the control unit is able to commandthe displacement of the focal point at a plurality of discretesonication points distributed along the trajectory. The control unit isable to command the energy generating means so that at each sonicationpoint they deposit a given quantity of energy that is the same from onesonication point to another. In this embodiment, it is the distributionof the sonication points on the trajectory which determines thedistribution of energy deposited in the target region.

The invention also relates to a method for heat treating an area ofbiological tissue in which the energy generating means supply energy toa focal point in said region, measuring means measure spatialtemperature distribution in said region, and a control unit commands themovement of the focal point along a pre-determined trajectory with aview to obtaining a spatial temperature distribution conforming to a setdistribution, characterized in that during the movement of the focalpoint the control unit commands the distribution of energy supplied bythe generating means along the trajectory in relation to measuredtemperature distribution and to the set distribution in accordance witha control law comprising a Proportional-Integral-Derivative term.

Other characteristics and advantages will become apparent from thefollowing description which is purely illustrative and non-limiting, andis to be read with respect to the appended figures in which:

FIG. 1 schematically shows an example of a heat treatment assemblyconforming to one embodiment of the invention,

FIG. 2 schematically illustrates the treatment steps performed by theheat treatment assembly,

FIG. 3 gives examples a and b of spatial profiles of set-pointtemperatures such as they can be commanded for a trajectory of spiralshape,

FIG. 4 shows an example of a trajectory in the form of an ellipticalspiral followed by the focal point of the energy generating means,

FIG. 5 comprises two diagrams respectively showing measured temperaturedistribution after the focal point of the energy generating means hasfollowed a spiral trajectory, and simulated temperature distribution fora uniform thermal diffusion coefficient in the tissues to be treated,

FIG. 6 is a curve showing the trend in temperature at the centre of thetarget region to be treated in relation to time, over a series of tensuccessive trajectories, the set temperature being 8° C. higher than theinitial temperature in the entire target region, during an ex vivoexperiment,

FIG. 7 shows the trend in parameters during each trajectory of theseries performed for FIG. 6, these parameters comprising: a coordinateof the focal point along one of the axes (Ox) of the reference point inwhich the trajectory is made, the ultrasound power deposited by theenergy generating means, the temperature profile measured in one sectionof the target region, and the temperature rise profile in the section ofthe target region,

FIG. 8 is a curve showing trend in temperature at the centre of thetarget region to be treated in relation to time, over a series of tensuccessive trajectories, the set temperature being 18° C. higher thanthe initial temperature in the entire target region, during an ex vivoexperiment,

FIG. 9 shows the trend in parameters during each trajectory of theseries performed for FIG. 8, these parameters comprising: a coordinateof the focal point along one of the axes (Ox) of the reference point inwhich the trajectory is performed, the ultrasound power deposited by theenergy depositing means, the profile of energy distribution in onesection of the target region, and the temperature rise profile measuredin the section of the target region,

FIG. 10 is a sample three-dimensional temperature map obtained using MRIimaging apparatus,

FIG. 11 is a curve showing temperature trend in the centre of the targetregion to be treated in relation to time, during an in vivo experiment,

FIG. 12 comprises three diagrams a, b and c respectively illustrating atheoretical spiral trajectory and showing an additional turn extendingoutside the target region to be treated, the projection of thesonication points of the additional turn on the contour of the targetregion, the actual trajectory comprising the projected sonication pointsof the additional turn.

In FIG. 1, the treatment assembly 1 shown comprises MRI imagingapparatus including a magnet 10. The assembly 1 comprises energygenerating means in the form of an annular-array probe 20 and amulti-channel generator 50 supplying the annular array probe 20. Theprobe 20 is integrated in the bed of magnet 10 and comprises generatingelements 21 able to emit ultrasounds in the direction of a focal point Pwhen the probe is supplied by the generator 50.

The annular-array probe 20 is for example a probe manufactured byUltrasonic (Besancon, France) having a radius of 80 mm, an openingdiameter of 96 mm and a variation in focal distance of between 60 and110 mm along the vertical axis. The ultrasound generating elements 21are able to emit at a frequency of approximately 1.5 MHz.

The energy generating means 20 can travel in the horizontal plane bymeans of a hydraulic travel system 30 with pistons 31 and 32 availablefrom LEP (Paris, France). This travel system 30 has laser guiding meansand its maximum travel speed is in the order of 3 mm per second, itseffective speed being 2 mm per second.

Assembly 1 also comprises a control unit 40 including a central unitwhose input is able to receive data from the MRI imaging apparatus and,in relation to such data, is able to command the travel system 30 tomodify the focal point P of the annular-array probe 20.

When in operation, the heat treatment assembly 1 is used to treat atarget region 60 of patient tissue. The control unit 40 commands themulti-channel generator 50 and the travel system 30 to perform the stepsshown FIG. 2.

Initially, the energy generating means 20 are arranged with respect tothe patient so that the focal point P is positioned at a point O locatedsubstantially in the centre of the target region 60 to be treated.

FIG. 2 schematically illustrates the treatment steps performed by theheat treatment assembly 1.

During a first step 100, the control unit 40 commands the travel system30 to position the focal point of the energy generating meanssuccessively at a plurality of sonication points along the firstpredetermined trajectory (j=1). The trajectory is of general ellipticalshape starting at the centre O of the target region and extendingoutwardly from this area. In addition, the control unit 50 commands theenergy generating means 20 so that, at each point of the plurality ofsonication points along the trajectory, they apply a quantity of givenenergy. The spiral shape of the trajectory allows energy to be depositedstarting at the centre O of the target region 60 and gradually extendingout to the edges of the target region. It will be understood that saidspiral trajectory promotes heat diffusion from the centre of the targetregion towards the edges of this area and enables benefit to be drawnfrom this diffusion to control temperature rise in the target region.

At a reference point (Ox, Oz) whose origin is the centre O of the targetregion 60, the parametric equation of the trajectory of focal point Pcan defined as follows:

$\begin{matrix}\left\{ \begin{matrix}{{x(\xi)} = {\Delta \; {a \cdot \frac{\xi}{2\; \pi} \cdot {\cos (\xi)}}}} \\{{z(\xi)} = {\Delta \; {b \cdot \frac{\xi}{2\; \pi} \cdot {\sin (\xi)}}}}\end{matrix} \right. & \lbrack 1\rbrack\end{matrix}$

in which (x, z) are coordinates of the focal point at reference point(Ox, Oz), Δa and Δb are the spaces between successive turns respectivelyfollowing axes Ox and Oz, and ξ is the parameter of the trajectory lyingbetween O and 2π·N, N being the number of turns of the ellipse.

During the first trajectory, the focal point P is moved so that the areaΩ added per unit of time to the region already treated is constant. Thiscoordination translates as the following differential equation withrespect to time t:

$\begin{matrix}{{\xi \cdot {\; \xi}} = {\frac{2\; {\pi \cdot \Omega}}{ɛ \cdot \left( {\Delta \; a} \right)^{2}}{t}}} & \lbrack 2\rbrack\end{matrix}$

in which Ω is the area added per unit of time to the region alreadycovered by the spiral trajectory and ε equals Δb/Δa and defines theeccentricity of the ellipse.

This first elliptical trajectory is formed of a plurality of discretesonications i, i ranging from 0 to n, whose positions with respect tothe centre O of the ellipse are defined by the vectors r₁=(x_(i),z_(i))in which i∈[0,n]. The focal point moves from one sonication position iat position r_(i) to the next i+1 at position r_(i+1) at a regular rate.The duration of sonication Δt is constant from one sonication point tothe next.

During a second step 200, the imaging apparatus measures the temperaturedistribution obtained T₁(x,z) in the target region.

If the tissues of the target region were fully homogeneous, i.e. theheat absorption and diffusion characteristics are uniform in the entiretarget region, the trajectory performed during the first step 100 wouldlead to a uniform increase in temperature in the target region.

Yet this is not the case, since treated tissues are generally nothomogeneous.

The measured temperature distribution is used to determine a meancoefficient of thermal diffusion D.

During a third step 300, the control unit, in relation to the measuredspatial distribution of temperature T₁(x,z), determines a secondtrajectory (j=2). This second trajectory has the same spiral shape asthe first trajectory. However, the speed of travel of the focal point ismodified according to a function of energy distribution R₂ dependent onposition (x,z) of the focal point on the trajectory, so that:

2  ( x  ( ξ ) , z  ( ξ ) ) · ξ ·  ξ = 2   π · Ω ɛ · ( Δ   a ) 2  t [ 3 ]

The effect of the distribution function R₂ is to modify the distancebetween two successive sonication points and hence the speed of travelof the focal point along the spiral trajectory. It is to be noted thatequation [3] is reduced to equation [2] when R₂ is replaced by R₁=1 overthe entire target region. The function R₂ is determined so as to offsetnon-homogeneities remaining after the first trajectory by modulating theenergy density delivered locally in the target region.

The time of each individual sonication is always Δt, so that the focalpoint travels from one sonication point to the next at the same rate asduring the first trajectory. The number n+1 of individual sonicationsalong the spiral trajectory is always the same.

During a fourth step 400, the control unit commands the travel system toposition the focal point of the energy generating means successively ata plurality of sonication points of the second trajectory.

Above-mentioned steps 200, 300 and 400 are optionally renewed to achievea number M of successive trajectories, so as to impose a set temperatureprofile upon the area to be treated during a predetermined treatmenttime. For each j-^(th) trajectory, the control unit determines a newdistribution function R_(j) and commands the travel system to cause thefocal point of the energy generating means move along the j-^(th)trajectory thus determined.

A general description is given below of the calculation step 300 of thedistribution function R_(j) calculated by the control unit.

It is considered that the control module commands the travel system andthe energy generating means so that the focal point of the energygenerating means travels over a number M of trajectories ofpre-determined shape.

The following designations are used:

-   O a reference point in the target region, e.g. located in the centre    of the target region:-   (Ox,Oz) a two-dimensional reference of origin O,-   θ_(j)(x,z) the set temperature to be reached at a point (x,z) over    the pathway of the j-^(th) trajectory.-   Tj(x,z) the temperature effectively measured at point (x,z) by the    MRI imaging apparatus after completion of the j-^(th) trajectory,-   R_(j) the distribution function determined for the j-^(th)    trajectory,-   G(D, τ) Green's function used to evaluate a variation in temperature    due to thermal diffusion D in the tissues (evaluated after the first    trajectory) over a time τ lapsed between two trajectories.

Green's function is described for example in the appended document“Local hyperthermia with MR-guided focused ultrasound: Spiral trajectoryof the focal point optimized for temperature uniformity in the targetregion”, Journal of Magnetic Resonance Imaging 12: 571-583 (published in2000). It's expression is:

${{G\left( {D,\sigma} \right)}\left( {r,r^{\prime}} \right)} = {\frac{1}{2 \cdot \pi \cdot \sqrt{2 \cdot D \cdot \tau}} \cdot {\exp\left( {- \frac{{{r - r^{\prime}}}^{2}}{4 \cdot D \cdot \tau}} \right)}}$

The efficacy of heating during the first trajectory can be expressed inthe form of a coefficient α₁ at point O:

$\alpha_{1} = \frac{\theta_{1}\left( {{x = 0},{z = 0}} \right)}{T_{1}\left( {{x = 0},{z = 0}} \right)}$

The spatial profile of the set temperature is given by:

$\begin{matrix}{{\theta_{j + 1}(r)} = {{{\eta_{j + 1} \cdot \frac{\theta_{1}(r)}{\alpha}}o\overset{.}{u}\; \alpha} \prec \eta_{j + 1} \leq 1}} & \lbrack 4\rbrack\end{matrix}$

In this equation, the value of η_(j+1) defines the desired trend intemperature between the j-^(th) and (j+1)-^(th) trajectory. η_(j+1)=1corresponds to a stationary temperature in the target region. That is tosay that the depositing of energy in the target region during the(j+1)-^(th) trajectory, defined by the distribution function R_(j+1)must solely offset heat losses due to heat conduction in the tissues.

The value of n_(j) is fixed for each trajectory j by means of aniterative algorithm, at the maximum value (between α and 1) for whichthe required power supplied by the energy generating means does notexceed a limit technical tolerance value of the instruments. The limittolerance value depends upon the energy generating means, this limitvalue is defined by the manufacturer of these energy generating means.

The temperature at a point r(x,z) which will be obtained aftercompletion of the (j+1)-^(th) trajectory can be evaluated as follows:

T _(i+1)(r)=[T _(j)

G(D,τ)](r)+

_(j+1)(r)·θ₁(r)   [5]

This temperature takes into account the heat diffusion between thej-^(th) and (j+1)-^(th) trajectory and the new distribution of energyR_(j+1). Green's function is always the same insofar as the coefficientof thermal diffusion D is assumed to be constant and the duration τ isthe same for each trajectory.

One condition for automatic control is: T_(j+1)=θ_(j+1)

Thereupon, it is deduced that:

_(j+1)(r)·θ₁(r)=θ_(j+1)(r)−[T _(j)

G(D,τ)](r)   [6]

_(j+1)(r)·θ₁(r)=[Tj(r)−[T _(j)

G(D,τ)](r)]+[θ_(j+1)(r)−θ_(j)(r)]+[θ_(j)(r)−T _(j)(r)]  [7]

This equation is the central equation of a control law of differentialand proportional type. Under the invention, this expression is modifiedto obtain a PID control law (Proportional Integral and Differential).The equation of this PID control law then becomes:

j + 1  ( r ) = [ T j  ( r ) - [ T j ⊗ G  ( D , τ ) ]  ( r ) ]  ( 1) + [ θ j + 1  ( r ) - θ j  ( r ) ]  ( 2 ) + a · [ θ j  ( r ) - T j ( r ) ]  ( 3 ) + a 2 4 · ∑ k = 0 j  [ θ j  ( r ) - T j  ( r ) ] ( 4 ) [ 8 ]

In equation [8] the first term (1) takes into account the variation intemperature due to heat diffusion in the tissues between two successivetrajectories j and j+1. The second term (2) is the differential term ofthe control law which takes into account the additional layer added tothe temperature profile by the (j+1)-^(th) trajectory. The third term(3) is the proportional term of the control law which takes into accountthe instantaneous error between the measured temperature and the settemperature defined for the preceding j-^(th) trajectory. Finally, thefourth term (4) is the integral term of the control law which takes intoaccount the errors between measured temperature and the set temperaturedefined for each of the previous trajectories. The parameter α is adimensionless magnitude related to the response time of the control loopof the travel system of the energy generating means. The response timeof the control loop is 2τ/α.

It is to be noted that the greater the parameter α, the more theautomatic control is sensitive to experimental noise with possiblefluctuations. A recommended value for parameter α is 2(√{square rootover (2−1)))}≈0.8284. This value leads to elimination of terms (3) and(4) in equation [8] when calculating R₂ after the completion of thefirst trajectory. The response time of the control loop then becomes2τ/α≈2.4143·τ which represents the time needed by the automatic controlto correct any error in measured temperature.

Equation [8] is equal to:

j + 1  ( r ) · θ 1  ( r ) = θ j + 1  ( r ) - [ T j ⊗ G  ( D , τ ) ] ( r ) - ( 1 - a ) · [ θ j  ( r ) - T j  ( r ) ] + a 2 4 · ∑ k = 0 j [ θ k  ( r ) - T k  ( r ) ] [ 9 ]

So that the time of a trajectory always remain constant, the trajectorycan be time dilated or compressed in time to bring its duration to valueτ. Simultaneously, the ultrasound power deposited by the energygenerating means is re-normalized in reverse direction by a factor whichis equal to the spatial average of R_(j+1) in the region underconsideration.

FIG. 3 shows examples a and b of spatial profiles R_(j)(r)·θ1(r) of settemperature such as they can be commanded for a trajectory of spiralshape. These examples are based on spiral trajectories having diametersof 12 mm and 16 mm respectively along axes Ox and Oz. The diffusioncoefficient D is 0.05 mm²/s. The trajectory comprises n+1=100 sonicationpoints, the sonications being spaced apart by Δt=1.6 s. Example arelates to a function of uniform distribution R₁(x,z)=1, while example bcorresponds to a distribution function R_(j) having a constant slope(constant gradient along axis Ox of −0.025 mm⁻¹).

FIG. 4 gives an example of an elliptical spiral trajectory followed bythe focal point of the energy generating means. The field of vision is128×128 mm² in image 1 whilst image 2 was magnified by a magnificationof 4. The spiral trajectory has diameters of 15 mm and 11 mmrespectively along axes Ox and Oz. The background image is obtained withthe gradient echo sequence used for MRI thermometry. Three samples ofagar gel can be seen in image 1. These samples allow three-pointcorrection of thermometry. Inhomogeneities can be seen in the structureof the treated sample.

In FIG. 5 the diagram shows the distribution of measured temperatureafter the focal point of the energy generating means has travelled overthe spiral trajectory shown FIG. 4. Diagram b shows simulatedtemperature distribution for a uniform coefficient of thermal diffusionD=0.13 mm²/s of the tissues to be treated. Diagram b is the diagramwhich is the closest to the experimental profile of diagram a. Thisdiagram b can be used to estimate the mean coefficient of thermaldiffusion in the target region to be treated.

FIG. 6 is a curve showing the trend in measured temperature at thecentre O of the target region in relation to time during ex vivoexperimenting. The measured temperature changes over a series of M=10successive trajectories. The set temperature is 8° C. in the entiretarget region (sublethal hyperthermia).

FIG. 7, in column one, shows the trend of coordinate x of the focalpoint of each of the ten trajectories of the series conducted during theexperimenting of FIG. 6. The second column indicates the ultrasoundpower deposited by the energy generating means during each of thetrajectories. The third column gives the temperature profile measured ina section of the target region passing though point O, the centre of thetarget region, after each trajectory. The fourth column gives theprofile of temperature rise measured in the section of the targetregion, obtained during each trajectory.

FIG. 8 is a curve showing the trend in measured temperature at thecentre O of the target region in relation to time during ex vivoexperiments. The measured temperature changes over a series of M=10successive trajectories. The set temperature is 18° C. higher than theinitial temperature in the entire target region (lethal hyperthermia)for the purpose of achieving thermal ablation.

FIG. 9, in column one, shows the trend of coordinate x of the focalpoint of each of the ten trajectories of the series conducted during theexperiments in FIG. 8. The second column indicates the ultrasound powerdeposited by the energy generating means during each of thetrajectories. The third column shows the profile of the distributionfunction R calculated in a direction passing through point O, the centreof the target region, after each trajectory. The fourth column shows theprofile of temperature rise measured in the section of the targetregion, obtained during each trajectory.

FIG. 10 is a sample three-dimensional temperature map obtained using MRIapparatus at the end of the sixth trajectory corresponding to FIG. 11.Experimental data was obtained with a spatial resolution of 1×1×5 mm³and smoothed by convolution with a two-dimensional Gaussian function ofstandard deviation of 1 mm in each direction (Ox) and (Oz). Temperaturedistribution cannot contain high spatial frequencies on account ofthermal diffusion.

FIG. 11 is a curve showing the trend in temperature at the centre O ofthe target region in relation to time during in vivo experimenting(diameter of the target region: 11 mm). The measured temperature risesover a series of M=6 successive trajectories. The dotted line representsthe set temperature rise (13 degrees Celsius above the physiologicaltemperature). The difference between two successive trajectories is 2minutes.

In FIG. 12 the diagram shows the positions of the different sonicationpoints along the first trajectory (j=1) and the limits of the targetregion to be treated (ellipse). As can be seen in this figure, thespiral trajectory gradually covers the target region. The trajectoryalso comprises an additional turn which extends outside the targetregion. This additional turn is in fact not actually executed by theenergy generating means. It is used solely to calculate the quantity ofenergy to be deposited at the frontier of the target region.

In FIG. 12, diagram b shows a step consisting of projecting thesonication points of the additional turn onto the contour of the targetregion (ellipse) in radial directions of projection.

In FIG. 12 diagram c shows the trajectory with the successive sonicationpoints such as it will be effectively conducted by the energy generatingmeans. This actual trajectory comprises the sonication points of theadditional turn projected onto the contour of the target region.

1. Heat treatment assembly for a region of biological tissue, comprising: energy generating means to supply energy at a focal point in the region, means for measuring the spatial temperature distribution in said region, a control unit comprising means able to command movement of the focal point along a predetermined trajectory with a view to obtaining a spatial temperature distribution conforming to a set distribution, wherein the control unit comprises means which, during the displacement of the focal point, are able to command distribution of the energy supplied by the generating means along the trajectory, in relation to measured temperature distribution and set distribution, in accordance with a control law comprising a Proportional-Integral-Derivative term.
 2. Assembly according to claim 1, wherein the control law takes into account a coefficient of thermal diffusion of the target region.
 3. Assembly according to claim 1, wherein the control unit (40) comprises means able to command movement of the focal point (P) along a series of successive trajectories (j) and, for each trajectory, to command a corresponding distribution of energy in relation to a set distribution associated with this trajectory and to temperature distributions measured during the preceding trajectories.
 4. Assembly according to claim 1, wherein to command energy distribution, the control unit comprises means able to determine a distribution function defining the position of the focal point along the trajectory in relation to time.
 5. Assembly according to claim 1, wherein the control unit comprises means able to command the displacement of the focal point at a plurality of discrete sonication points distributed along the trajectory.
 6. Assembly according to claim 5, wherein the control unit comprises means able to command the energy generating means so that they deposit at each sonication point a given quantity of energy that is equal from one sonication point to the next.
 7. Assembly according to claim 1, wherein the control unit comprises means able to command the movement of the focal point along a series of successive trajectories and, for each trajectory, to command a corresponding energy distribution such that: j + 1  ( r ) · θ 1  ( r ) = θ j + 1  ( r ) - [ T j ⊗ G  ( D , τ ) ]  ( r ) - ( 1 - a ) · [ θ j  ( r ) - T j  ( r ) ] + a 2 4 · ∑ k = 0 j  [ θ k  ( r ) - T k  ( r ) ] in which r is the position of a point in the target region, θ₁ is the set temperature distribution to be reached during the conducting of the first trajectory, θ_(j) is the set temperature distribution to be reached during the conducting of the j-^(th) trajectory, T_(j) is the temperature distribution effectively measured by the measurement means after the completion of the j-^(th) trajectory, G(D,τ) is Green's function which depends on the thermal diffusion D in the target region over a period of time r lapsed between two trajectories j and j+1 α is a dimensionless parameter for automatic control.
 8. Assembly according to claim 1, wherein the control unit comprises means able to move the focal point along a trajectory of general spiral shape.
 9. Assembly according to claim 1, wherein the control unit comprises means able to command displacement of the focal point in relation to a set temperature distribution that is uniform in the target region.
 10. Assembly according to claim 1, wherein the control unit comprises means able to command displacement of the focal point in relation to a set temperature distribution having a uniform gradient in one direction in the target region.
 11. Method for heat treating a region of biological tissue, wherein energy generating means supply energy to a focal point in said region, measurement means measure spatial temperature distribution in said region, and a control unit commands movement of the focal point along a predetermined trajectory to obtain a spatial temperature distribution conforming to a set distribution, and wherein during the displacement of the focal point the control unit commands the distribution of energy supplied by the generating means along the trajectory, in relation to the measured temperature distribution and the set distribution, in accordance with a control law comprising a Proportional-Integral-Derivative term. 